Mast cell–dependent CD8þ T-cell recruitment mediates immune surveillance of intestinal tumors in ApcMin/þ Mice

Sobha R. Bodduluri, Steven Mathis, Paramahamsa Maturu, Elangovan Krishnan, Shuchismita R. Satpathy, Paula M. Chilton, Thomas C. Mitchell, Sergio Lira, Massimo Locati, Alberto Mantovani, Venkatakrishna R. Jala, Bodduluri Haribabu

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


The presence of mast cells in some human colorectal cancers is a positive prognostic factor, but the basis for this association is incompletely understood. Here, we found that mice with a heterozygous mutation in the adenomatous polyposis coli gene (ApcMin/þ) displayed reduced intestinal tumor burdens and increased survival in a chemokine decoy receptor, ACKR2-null background, which led to discovery of a critical role for mast cells in tumor defense. ACKR2/ApcMin/þ tumors showed increased infiltration of mast cells, their survival advantage was lost in mast cell–deficient ACKR2/SA/ApcMin/þ mice as the tumors grew rapidly, and adoptive transfer of mast cells restored control of tumor growth. Mast cells from ACKR2/ mice showed elevated CCR2 and CCR5 expression and were also efficient in antigen presentation and activation of CD8þ T cells. Mast cell–derived leukotriene B4 (LTB4) was found to be required for CD8þ T lymphocyte recruitment, as mice lacking the LTB4 receptor (ACKR2/BLT1/ApcMin/þ) were highly susceptible to intestinal tumor-induced mortality. Taken together, these data demonstrate that chemokine-mediated recruitment of mast cells is essential for initiating LTB4/BLT1-regulated CD8þ T-cell homing and generation of effective antitumor immunity against intestinal tumors. We speculate that the pathway reported here underlies the positive prognostic significance of mast cells in selected human tumors.

Original languageEnglish
Pages (from-to)332-347
Number of pages16
JournalCancer Immunology Research
Issue number3
StatePublished - 1 Mar 2018


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